2023 World Conference on Lung Cancer (Posters)-P1.12. Sensitization of Cancer Cells to Tumor Treating Fields (TTFields) via Inhibition of the PI3K/AKT Signaling Pathway

P1.12. Sensitization of Cancer Cells to Tumor Treating Fields (TTFields) via Inhibition of the PI3K/AKT Signaling Pathway - PDF(Slides)

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This research study aimed to understand the molecular mechanism behind the activation of the PI3K/AKT signaling pathway following the application of Tumor Treating Fields (TTFields) therapy. TTFields are a type of electric fields that disrupt cellular processes essential for cancer cell viability and tumor progression. TTFields therapy is currently approved for the treatment of glioblastoma, recurrent glioblastoma, and unresectable pleural mesothelioma.<br /><br />In this study, the researchers applied TTFields to different cancer cell lines, including glioblastoma, ovarian cancer, and non-small cell lung carcinoma. They observed an activation of the PI3K/AKT pathway, indicated by increased phosphorylation of AKT, both in vitro and in vivo experiments.<br /><br />The researchers also investigated the role of Focal Adhesion Kinase (FAK) and its upstream activator ROCK in the activation of the PI3K/AKT pathway. They found that inhibiting ROCK during TTFields application decreased TTFields-induced FAK phosphorylation, and inhibiting FAK during TTFields application decreased TTFields-induced AKT phosphorylation.<br /><br />Furthermore, the study showed that inhibition of PI3K during TTFields application augmented the treatment efficacy. They observed a decrease in cell count and colony formation when PI3K was inhibited along with TTFields application. Additionally, they found that inhibition of PI3K increased the effectiveness of TTFields against tumors in in vivo experiments.<br /><br />In conclusion, this study provides insight into the molecular mechanism of PI3K/AKT pathway activation following TTFields application. The findings suggest that targeting the PI3K/AKT pathway can enhance the sensitivity of cancer cells to TTFields therapy, potentially improving its effectiveness in treating various solid tumors.

Asset Subtitle

Moshe Giladi

Meta Tag

Speaker Moshe Giladi

Topic Tumor Biology: Translational Biology - Translational Therapeutics

Keywords

molecular mechanism

PI3K/AKT signaling pathway

Tumor Treating Fields therapy

TTFields

glioblastoma

ovarian cancer

non-small cell lung carcinoma

phosphorylation of AKT

Focal Adhesion Kinase

inhibition of PI3K